Institute of Cardiovascular Disease Research, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
Sci Rep. 2020 Sep 21;10(1):15407. doi: 10.1038/s41598-020-72325-8.
The sarco/endoplasmic reticulum Ca ATPase 2a (SERCA2a) is responsible for calcium transport during excitation-contraction coupling and is essential for maintaining myocardial systolic/diastolic function and intracellular Ca levels. Therefore, it is important to investigate mechanisms whereby luteolin modulates SERCA2a expression to attenuate myocardial ischemia/reperfusion injury. C57BL/6j mice were randomly divided into eight groups. The expression and activity of SERCA2a was measured to assess interactions between the SERCA2a promoter and the Sp1 transcription factor, and the regulatory effects of luteolin. We used serum LDH release, serum cardiac troponin I level, hemodynamic data, myocardial infarction size and apoptosis-related indices to measure SERCA2a cardio-protective effects of luteolin pretreatment. Sp1 binding to SERCA2a promoter under ischemia/reperfusion conditions in the presence or absence of luteolin was analyzed by chromatin immunoprecipitation. Our experimental results indicated that during myocardial ischemia/reperfusion injury, luteolin pretreatment upregulated the expression levels of SERCA2a and Sp1. Sp1 overexpression enhanced the expression of SERCA2a at the transcriptional level. Luteolin pretreatment reversed the expression of SERCA2a through the increased expression of Sp1. Moreover, we demonstrated that luteolin pretreatment appeared to exert myocardial protective effects by upregulating the transcriptional activity of SERCA2a, via Sp1. In conclusion, during myocardial ischemia/reperfusion, Sp1 appeared to downregulate the expression of SERCA2a. Luteolin pretreatment was shown to improve SERCA2a expression via the upregulation of Sp1 to attenuate myocardial ischemia/reperfusion injury.
肌浆网/内质网 Ca2+-ATP 酶 2a（SERCA2a）负责兴奋-收缩偶联过程中的钙转运，对维持心肌收缩/舒张功能和细胞内 Ca 水平至关重要。因此，研究木樨草素调节 SERCA2a 表达从而减轻心肌缺血/再灌注损伤的机制非常重要。将 C57BL/6j 小鼠随机分为 8 组。通过测量 SERCA2a 的表达和活性，评估 SERCA2a 启动子与 Sp1 转录因子之间的相互作用，以及木樨草素的调节作用。使用血清 LDH 释放、血清心肌肌钙蛋白 I 水平、血流动力学数据、心肌梗死面积和凋亡相关指标，来衡量木樨草素预处理对 SERCA2a 的心脏保护作用。通过染色质免疫沉淀分析缺血/再灌注条件下 Sp1 与 SERCA2a 启动子的结合。实验结果表明，在心肌缺血/再灌注损伤过程中，木樨草素预处理上调了 SERCA2a 和 Sp1 的表达水平。Sp1 过表达增强了 SERCA2a 在转录水平的表达。木樨草素预处理通过 Sp1 表达的增加逆转了 SERCA2a 的表达。此外，我们证明木樨草素预处理通过上调 Sp1 来增强 SERCA2a 的转录活性，从而发挥心肌保护作用。总之，在心肌缺血/再灌注期间，Sp1 似乎下调了 SERCA2a 的表达。木樨草素预处理通过上调 Sp1 来改善 SERCA2a 的表达，从而减轻心肌缺血/再灌注损伤。
